Osteoarthritis treatment and device

ABSTRACT

A method for treating arthritis of a joint includes identifying a bone lesion in a bone adjacent to the joint; and implanting in the bone a reinforcing member in or adjacent to the bone lesion. A kit for conducting the method includes: (a) at least one reinforcing member having a proximal face adapted to face the joint, a distal face adapted to face away from the joint, and a wedge-shaped edge adapted to pierce bone, wherein the at least one reinforcing member is planar and sterile; and (b) a container adapted to maintain the at least one reinforcing member sterile. Another kit includes: (a) a sterile fluid; (b) a syringe for injecting the fluid into a bone; (c) a curing agent adapted to cure the fluid to polymerize and/or cross-link; and (d) a container adapted to maintain the sterility of contents of the container.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation of U.S. patent application Ser. No. 13/269,136filed on Oct. 7, 2011 and entitled “OSTEOARTHRITIS TREATMENT ANDDEVICE,” which is a divisional of U.S. patent application Ser. No.12/110,434, now U.S. Pat. No, 8,062,364, filed on Apr. 28, 2008 andentitled “OSTEOARTHRITIS TREATMENT AND DEVICE,” which application claimspriority to U.S. Provisional Application No. 60/914,465, filed on Apr.27, 2007 and entitled “OSTEOARTHRITIS TREATMENT AND DEVICE,” thecontents of which are herein incorporated by reference in theirentirety.

FIELD

This invention relates to a method d device for treating osteoarthritis,particularly osteoarthritis of the knee.

BACKGROUND

Osteoarthritis is the most common form of arthritis, affecting thehands, knees, hips, spine and other joints. Characteristics ofosteoarthritis include a loss of cartilage, seen as a reduction in thejoint space, and osteophytes (or bone spurs).

Arthritic pain is a leading cause of lost productivity. The cause ofarthritic pain is unclear. The amount of cartilage loss correlatespoorly with the severity of pain in an afflicted individual. Likewise,radiographic finding such as osteophytes (bone spurs) and thickening ofsubchondral bone (eburination) do not correlate with the presence orseverity of pain.

Bone marrow lesions (or edemas) are very strongly associated with kneearthritis pain (Felson et al., “The association of bone marrow lesionswith pain in knee osteoarthritis,” Ann Intern Med. 2001 Apr. 3;134(7):541-9) and disease progression (Felson et al., “Bone marrow edemaand its relation to progression of knee osteoarthritis.” Ann Intern Med.2003 Sep. 2; 139(5 Pt 1):330-6). See also U.S. Pat. No, 6,564,083 toStevens, which describes a method of identifying in a patient havingjoint pain the susceptibility of the patient to developing progressiveosteoarthritis or loss of joint space, by determining the presence orabsence of bone marrow edema about or of the joint. The determination ispreferably made through the use of Magnetic Resonance Imaging (MRI).

The nature and cause of bone marrow lesions is poorly understood.Histologic examination of these lesions demonstrates abnormal bone witharea of fibrosis, osteonecrosis and extensive bone remodeling (Zanettiet al., “Bone Marrow Edema Pattern in Osteoarthritic Knees: Correlationbetween MR Imaging and Histologic Findings,” Radiology, 2000;215:835-840). It has been suggested that they are related toinflammation (Bollet, “Edema of the bone marrow can cause pain inosteoarthritis and other diseases of bone and joints.” Ann Intern Med.2001 Apr. 3; 134(7):591-3), venous hypertension (Arnoldi et al.,“Intraosseous phlebography, intraosseous pressure measurements and99mTc-polyphosphate scintigraphy in patients with various painfulconditions in the hip and knee.” Acta Orthrop Scand. 1980; 51:19-28), orimpaired arterial blood flow (McAlindon et al., “Magnetic resonanceimaging in osteoarthritis of the knee: correlation with radiographic andscintigraphic findings.” Ann Rheum. Dis. 1991; 50:14-9. Others havesuggested these lesions reflect increased bone stress and microfractureof the bone (see Felson et al. 2003, supra).

Knee arthritis affects millions of people and the pain associated withthis disease can be disabling. Patients who initially present withpainful knee arthritis are usually treated non-surgically. Non-surgicaltreatments are modestly effective at temporarily relieving pain, but notrisk free. Pharmacologic intervention (i.e., non-steroidalanti-inflammatory drugs) has been reported to be associated withsignificant complications, such as gastric ulcers, strokes and heartattacks. Steroid or viscosupplement injection may lead to infection.Steroid injections may also have systemic effects such as increasedblood sugar and hypertension. Generally speaking non-surgicalinterventions are most efficacious for early arthritic disease and donot prevent disease progression.

When patients fail non-surgical treatment, surgical intervention isoften recommended. Arthroscopic surgery has been shown to have limitedeffectiveness and has a small role in the management of knee arthritis.More invasive surgical approaches such as high tibial osteotomy andpartial or complete knee replacement predictably relieve pain. However,these major operations are also potentially associated with significantmorbidity and occasional mortality. These risks along with the limiteddurability of implantable devices influence patient and physicians todefer surgery until the symptoms become unbearable.

Accordingly, it is desired to provide an effective, surgical treatmentof osteoarthritis, and particularly knee arthritis pain. It is furtherdesired that such surgical treatment be less invasive than high tibialosteotomy and partial or complete knee replacement.

All references cited herein are incorporated herein by reference intheir entireties.

SUMMARY

Accordingly, a first aspect of the invention comprises a method fortreating arthritis of a joint, said method comprising: identifying abone lesion in a bone adjacent to the joint; and implanting in the bonea reinforcing member in or adjacent to the bone lesion. The reinforcingmember as implanted is preferably free of artificial bones to the bone.The method preferably decreases pain associated with arthritis and/orslows the progression of arthritis.

A second aspect of the invention comprises a kit for treating arthritisof a joint, said kit comprising: (a) at least one reinforcing membercomprising a proximal face adapted to face the joint, a distal faceadapted to face away from the joint, and a wedge-shaped edge adaptedpierce bone, wherein the at least one reinforcing member is planar andsterile; and (b) a container adapted to maintain the at least onereinforcing member sterile.

A third aspect of the invention comprises a kit for treating arthritisof a joint, said kit comprising: (a) a sterile fluid; (b) a syringe forinjecting the fluid into a bone; (c) a curing agent adapted to cure thefluid to polymerize and/or cross-link; and (d) a container adapted tomaintain the sterility of contents of the container.

A fourth aspect of the invention comprises a method for treatingarthritis of a joint, said method comprising: (a) identifying a bonelesion in a bone adjacent to the joint; and (b) implanting in the bone areinforcing member in or adjacent to the bone lesion, wherein the methodstabilizes the bone in order to prevent further biomechanical breakdownof the bone and of adjacent meniscal tissues, and alleviates pain in thejoint.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be described in conjunction with the followingdrawings in which like reference numeral designate like elements andwherein:

FIG. 1 is a magnetic resonance image (2D IR 1900/90/25.0; COR 200×180;4.O FFS; 256×144 pr.) of an arthritic knee on which is overlaid a sideview of an embodiment of the reinforcing member of the invention;

FIGS. 2A, 2B and 2C are overhead views of three embodiments of thereinforcing member of the invention; and

FIG. 2D is a side view of the embodiment of FIG. 2B.

DESCRIPTION OF THE EMBODIMENTS

The invention is based on our theory that bone marrow lesions detectedby MRI represent overstressed bone. Bone is continuously fatigued anddamaged by everyday activity. However, bone is a living tissue and bonerepair occurs in concert. Certain pathological processes, such as lossof joint cartilage, can disturb the equilibrium between bone damage andbone repair. Cartilage protects underlying bone shielding it fromstress. In addition, loss of cartilage leads to joint deformity furtherincreasing bone stress. Overstressed bone sustains more damage thanrepair, which results in pain.

The invention enhances the strength of bone, shielding bone fromexcessive stress. Strengthening the bone in accordance with theinvention shifts the damage/repair equilibrium toward repair. Inaddition, strengthening the bone reduces, reverses and/or prevents thedeformation of overstressed bone, which should relieve pain and slowarthritic disease progression within the underlying bone and adjacentmeniscal tissues (cartilage).

The invention provides an additional treatment option for patientssuffering with arthritic pain, particularly in the knee. Thoseindividuals who have exhausted non-surgical care, but are notsymptomatic enough or not prepared for other reasons (emotional,financial, etc.) to undergo more major surgical interventions, are idealfor treatment using the present invention. The method of the inventionshould be considered minor or outpatient surgery. The risk ofcomplications if expected to be significantly less than with majorarthritic surgery, such as high tibial osteotomy and partial or totalknee replacement. Preferred embodiments of the inventive treatmentstabilize the defect in the subchondral (underlying) bone in order toprevent further biomechanical breakdown of the bone and of the adjacentmeniscal tissues, and alleviate the corresponding pain in the joint.

The method of the invention comprises identifying a bone lesion in abone adjacent to the joint, and implanting in the bone a reinforcingmember in or adjacent to the bone Lesions. Referring to FIG. 1, anarthritic human knee comprises femur 10 and tibia 12. Bone lesion 14 oftibia 12 presents as a focally increased signal in the marrow in an MRIof the knee. In certain embodiments, coronal spin-echo fat-saturatedproton density and T2-weighted fat-saturated magnetic resonance imagesare preferred. Bone lesions thought to be associated with arthritis areless than 10 cm or 5 cm or 1 cm from the joint. Thus in preferredembodiments, the invention treats bone lesions which are from 0 to 10 cmfrom the joint, or 0 to 5 cm from the joint, or 0 to 1 cm from thejoint.

The bone lesion is preferably identified using MRI, but in lesspreferred embodiments, other identification means may be employed. Forexample, bone lesions can be identified using Technetium-99 bone scans,because there is a close correlation between the presence of activitynoted on Technetium-99 bone scans and bone marrow lesions. Inembodiments of the invention employee MRI, any MRI technology thatreveals bone marrow lesions can be used, for example, open MRI, lowfield strength MRI, extremity MRI, whole body scanner MRI or the like.

Reinforcing member 14 is preferably selected in accordance with theguidance provided by the following bone lesion grading system.

Bone Lesion Grading System Bone Lesion Class Dimension Comments I  <1 mmBone healing is likely and resorbable graft materials are appropriate.Non-limiting exemplary materials for use as the reinforcing memberinclude hyaluronic acid (HA), calcium phosphate (CaP) grafts, andcements (CaP & PMMA). II 1-3 mm Bone healing is more challenging and asemi-structural graft material is appropriate. Non-limiting exemplarymaterials for use as the reinforcing mbmer include HA, CaP, cements (CaP& PMMA), and structural implants of metal and/or polymer. III 3-5 mmBone healing is less likely, and thus structural non-resorbing supportis appropriate. Non-limiting exemplary materials for use as thereinforcing member include CaP cements, PMMA cements, and structuralimplants of metal and/or polymer. IV  >5 mm Bone healing is unlikely,and thus a permanent structural implant is required. Non-limitingexemplary materials for use as the reinforcing member include PMMAcements, and structural implants of metal and/or polymer.

FIG 1 shows a preferred example of how reinforcing member 16 could beimplanted in bone lesion 14. It is also within the scope of theinvention to implant the reinforcing member adjacent to the bone lesion.For example, the reinforcing member can be implanted adjacent to a sideof the bone lesion proximal to the joint and/or adjacent to a side ofthe bone lesion distal to the joint. One or more than one reinforcingmember can be implanted in and/or adjacent to a bone lesion. Areinforcing member is adjacent to a bone lesion if it is less than 10 cmaway from an outer surface of the bone lesion. Adjacent reinforcingmembers can be in contact with an outer surface of the bone lesion. Thusin preferred embodiments, an adjacent reinforcing member can be from 0to 10 cm from the bone lesions, or 0 to 5 cm from the bone lesion, or 0to 1 cm from the bone lesion.

It is also preferred that the reinforcing member as implanted be free ofbonds to the bone. Thus, the reinforcing member is preferably not, forexample, glued, cemented, stapled, stitched, clamped or screwed to thebone. However, the expression “free of artificial bonds to the bone”does not exclude from such embodiments the possibility that bonds areformed by biological processes in situ.

The reinforcing member is implants in the bone in or adjacent the bonelesion such that a proximal face faces the joint and a distal face facesaway from the joint. Preferably, the reinforcing member is selected ormodified (e.g., cut, torn, etc.) such that a maximum dimension of theproximal face exceeds a maximum dimension of the bone lesion. It is alsowithin the scope of the invention for the maximum dimension of the bonelesion to equal or exceed a maximum dimension of the proximal face.Thus, the reinforcing member can be larger, smaller or the same size asthe bone lesion. The reinforcing member is preferably implanted suchthat the proximal face is perpendicular to a longitudinal axis of thebone. It is preferred that the proximal and/or distal faces be theprimary load bearing surfaces.

In certain embodiments, a syringe (optionally with a needle) can be usedto inject a fluid into a bone so as to form the reinforcing member insitu. This step can be conducted with or without first creating anopening in the bone. The fluid is preferably a liquid, semi-solid, gel,hydrogel, dispersion or slurry. After injection, the fluid can remain inits originally-injected state, or can cure to a less fluid state. Forexample, the injected fluid can cross-link or polymerize from a liquidto form a semi-solid, gel or solid. Fluids that cure in situ can beself-curing or can cure in response to curing means, such as, e.g.,radiation (e.g., UV light), heat (e.g., body temperature), moistureand/or a curing agent. See, e.g., U.S. Pat. No. 6,818,018 to Sawhney andU.S. Pat. No. 6,280,474 to Cassidy et al.

In certain embodiments, the reinforcing member is a solid or a non-fluidmaterial that is not amenable to injection in to the bone. In theseembodiments, the surgeon creates a small opening in the vicinity of thebone lesion. Suitable surgical tools for this task include standard boneinstruments (e.g., chisels, drills, etc.) and instruments specificallydesigned for use in the method of the invention. It is also possible touse the wedge-shaped edge of the reinforcing member to pierce the bone,preferably with assistance from a hammer.

Although it is within the scope of the invention for the surgeon toimplant the reinforcing member by studying a previously captured imageof the bone lesion and using his or her own senses to estimate thelocation and boundaries of the bone lesion, it is preferred that thesurgeon be provided with additional guidance during surgery. Forexample, surgery can be conducted using real-time imaging, roboticdevices, braces for maintaining the joint in a position consistent withcaptured images of the joint and/or labels, See, e.g., U.S. Pat. No.6,711,432 to Krause et al. Suitable labels include but are not limit toradioactive labels, such as Technetium-99 and objects, such as fiducialmarkers.

Postoperatively, patients may be required to maintain partial weightbearing and use ambulatory aids. Depending upon the physician'sdirection, full weight bearing may be possible. Routine postintervention physical therapy will likely be required. Additionally,patients will need routine post intervention care, observation andfollow-up.

FIG. 2 shows several different embodiments of reinforcing members of theinvention. FIG. 2A shows reinforcing member 16 having a triangularprofile, FIG. 2B shows reinforcing member 16 having a rectangularprofile and FIG. 2C shows reinforcing member 16 having is circularprofile. Reinforcing member 16 is preferably planar, as seen from FIG.2D, which shows a side view of the rectangular embodiment of FIG. 2C.The term “planar” as used herein refers to three-dimensional objectswhich are relatively long in two dimensions and relatively short in athird dimension. Planar reinforcing members in accordance with theinvention can have a thickness which is ≦50% of the length and ≦50% ofthe width of a rectangular reinforcing member (or ≦50% of the diameterin the case of a circular reinforcing member or ≦50% of the height and≦50% of the base in the case of a triangular reinforcing member).

As can be best seen in FIG. 2D, reinforcing member 16 has wedge-shapededge 18 on at least one edge thereof. Wedge-shaped edge 18 is adapted tofacilitate the step of driving reinforcing member 18 into the bone.Thus, the particular angle and other dimensions of the wedge aredictated by factors that are known in the art. Preferably, wedge-shapededge 18 is similar to that found on standard surgical tools such asosteotomes or on implants such as blade plates or osteotomy staples.

Reinforcing member 16 comprises a physiologically compatible materialthat has sufficient durability to reinforce the overstressed bone of thebone lesion and bear physiologic loads. Preferred materials for thereinforcing member include metals, such as titanium, stainless steel,alloys of cobalt and chrome, tantalum, alloys of titanium and nickel andother superelastic metal alloys, such as taught by U.S. Pat. No.6,527,810. Titanium “foam”, tantalum, trabecular metals, nanoceramics orother hightly porous nanomaterials, and chrome cobalt are particularlypreferred. Other embodiments comprise the use of bone, such asautografts, allografts, and artificial or synthetic bone substitutes.Certain embodiments comprise the use of polymeric materials.

Reinforcing member 16 is preferably osteogenic, osteoconductive and/orosteoinductive. The term “osteogenic” as used herein refers to theability of the reinforcing member to promote the growth of new bonetissue. The term “osteoinductive” as used herein refers to the abilityof the reinforcing member to recruit cells from the host that have thepotential for forming new bone and repairing bone tissue. The term“osteoconductive” as used herein refers to the ability of anon-osteoinductive reinforcing member to serve as a substrate supportingbone growth. Osteoconductive materials that are suitable for use in thepresent invention are biologically acceptable and include but are notlimited to collagen and the various forms of calcium phosphatesincluding hydroxyapatite, tricalcium phosphate, and fluorapatite.Suitable osteoinductive substances include but are not limited to bonemorphogenetic proteins (e.g., rhBMP-2), demineralized bone matrix,transforming growth factors (e.g., TGF-beta), osteoblast cells, andvarious other organic species known to induce bone formation. Theosteoconductive and osteoinductive properties may be provided by bonemarrow, blood plasma, or morselized bone of the patient, or commerciallyavailable materials. Osteoinductive materials such as BMP may be appliedto articles of the invention, for example, by immersing the article inen aqueous solution of this material in a dilute suspension of type Icollagen. Osteoinductive materials such as TGF-beta may be applied to anarticle of the invention from a saline solution containing an effectiveconcentration of TGF-beta, or may be carried in the resilient material.

The reinforcing member can be resorbable, but is preferablynon-resorbable, particularly when used to treat a chronic condition,such as osteoarthritis.

In certain embodiments, electrical stimulation is applied to the bone topromote bone healing.

The reinforcing member can be provided alone or in a kit according tothe invention. A first embodiment of the kit includes at least onereinforcing member, which is sterile, and a container adapted tomaintain the sterility of the at least one reinforcing member.Preferably, the containers are sealed flexible bags. The term “sterile”as used herein denotes a condition in which an object has a sterilityassurance level (SAL) or 10⁻³ or less (preferably 10⁻⁶ of less) inaccordance with current FDA guidelines for medical devices and asmeasured by AAMI/ISO 11607-1.

The first embodiment of the kid can optionally include an assortment ofreinforcing members of various sizes and/or shapes appropriate for usewith a variety of bone lesions. The kit can also include instructionsfor use, e.g., printed on the container and/or on inserts within thecontainer. The kit can still further include a tool for adjusting thesize of the reinforcing member, a hammer for driving the reinforcingmember into the bone and/or a bone filler to seal the open end of thechannel in the bone in which the reinforcing member resides. Suitablebone fillers include but are not limited to materials comprisingbeta-tricalcium phosphate (e.g., VITOSS, PROOSTEON 500R made byE-Interpore-Cross International), hydroxyapatite (e.g., OSTEOGRAF madeby Ceramed Dente, Inc., Lakewood, Colo.), calcium carbonate, calciumsulfate (e.g., OSTEOSET and ALLOMATRIX made by Wright MedicalTechnology, Inc.), calcium phosphate (e.g., CALCIBON made by Merck &Co., Inc., Whitehouse Station, N.J. and NORIAN SRS made bySynthes-Strates, Switzerland), synthetic bone fillers (e.g., CORTOSS)and/or processed bone fillers (e.g., BIOOSS made by GeistlichBiomaterials, Inc., Switzerland). See U.S. Pat. No. 7,166,570.

A second embodiment of the kit includes a fluid, a syringe for injectingthe fluid into a bone and a container adapted to maintain the sterilityof the contents of the container. This embodiment of the kit can furthercomprise a needle and premeasure portions of ingredients in a pluralityof separate vials. As with the first embodiment of the kit, thisembodiment can optionally include instructions for use, e.g., printed onthe container and/or on inserts within the container. The kit canfurther include bone tools for providing a channel in the bone in whichthe fluid is injected and/or a bone filler to seal the open end of thechannel in he bone in which the reinforcing member resides. The kit caninclude curing agents (i.e., polymerizing agents, catalysts and/orcrosslinking agents) as separate ingredients to be added to the injectedfluid. The kit can include other curing means, such as a UV light sourceor other device for generating radiation. The fluid can be preloaded inthe syringe for injection. In some embodiments, a multiple barrelsyringe can be included for in situ mixing of ingredients that must bestored separately in different barrels of the syringe (e.g., monomersand polymerizing agent, or polymers and crosslinking agent, etc.).

While the invention is described in the context of osteoarthritis of theknee, it is not limited to such condition. Other conditions that can betreated in accordance with the invention include but are not limited toosteoarthritic of joints other than the knee.

While the invention has been described in detail and with reference tospecific examples thereof, it will be apparent to one skilled in the artthat various changes and modifications can be made therein withoutdeparting from the spirit and scope thereof.

1-16. (canceled)
 17. A method of reinforcing bone located in a targetedbone marrow lesion in a subchondral region of a first bone adjacent aknee joint for treating the targeted bone marrow lesion, the methodcomprising: identifying a bone marrow lesion less than 10 cm from a kneejoint so as to establish a targeted bone marrow lesion for receivingtreatment, the targeted bone marrow lesion occurring in a subchondralregion of a first bone adjacent the knee joint, the subchondral regionof the first bone occurring under an articular surface of the firstbone; creating, in the first bone that contains the targeted bone marrowlesion in the subchondral region, a subchondral injection path to anarea in or adjacent to the targeted bone marrow lesion for injecting aninjectable fluid material into said area for reinforcing bone located inthe targeted bone marrow lesion, wherein said creating preserves anexisting condition of the overlying articular cartilage of the firstbone adjacent the knee joint; and injecting an injectable and curablefluid material into said area via the subchondral injection path,wherein the injectable fluid material is a bone reinforcing materialthat is left in the area for becoming less fluid in the area so as toform, in situ, a bone reinforcing member for reinforcing bone located inthe targeted bone marrow lesion.
 18. The method of claim 17, whereinsaid identifying includes identifying the bone marrow lesion through useof magnetic resonance imaging (MRI) of the knee joint.
 19. The method ofclaim 18, wherein said identifying the bone marrow lesion through use ofmagnetic resonance imaging (MRI) of the knee joint is viewing the bonemarrow lesion on an MRI of the knee joint.
 20. The method of claim 17,wherein said identifying includes identifying with non-MRIidentification means.
 21. The method of claim 17, wherein said creatingis conducted without further creating a void inside the first bone in oradjacent to the targeted bone marrow lesion.
 22. The method of claim 17,wherein said area is in the targeted bone marrow lesion.
 23. The methodof claim 17, wherein said area is adjacent to the targeted bone marrowlesion.
 24. The method of claim 17, wherein said area is up to 5 cm fromthe targeted bone marrow lesion.
 25. The method of claim 17, wherein thetargeted bone marrow lesion is less than 5 cm from the knee joint. 26.The method of claim 25, wherein the targeted bone marrow lesion is lessthan 1 cm from the knee joint.
 27. The method of claim 17 providing onlya single bone reinforcing member in said area.
 28. The method of claim17, wherein said injectable fluid material includes a calcium phosphate.29. The method of claim 28, wherein said calcium phosphate comprises acalcium phosphate cement.
 30. The method of claim 17, wherein saidinjecting includes injecting the injectable fluid material from apre-loaded syringe.
 31. The method of claim 30, wherein said pre-loadedsyringe includes a needle.
 32. The method of claim 17, wherein saidinjectable fluid material includes a non-resorbable material.
 33. Themethod of claim 17, wherein the injectable fluid material is left in thearea without also delivering a solid structural implant to the area inaddition to the injectable fluid material.
 34. The method of claim 17,wherein the targeted bone marrow lesion is in a proximal tibia.
 35. Themethod of claim 17, wherein the targeted bone marrow lesion is in adistal femur.